Serotonin transporter (5-HTTLPR) genotype, childhood abuse, and suicide attempts in adult psychiatric inpatients

There is growing evidence that a functional polymorphism in the serotonin transporter gene (5-HTTLPR) moderates the impact of negative life events (e.g., childhood abuse) on the development of depression. However, it is unclear whether the gene x environment interaction predicts suicide attempts specifically. In addition, previous studies have not examined different forms of childhood abuse separately. In the current study, we found that 5-HTTLPR genotype moderated the link between childhood physical and sexual, but not emotional, abuse and adult psychiatric inpatients' histories of suicide attempts.     

Serotonin transporter genetic variation and biased attention for emotional word stimuli among psychiatric inpatients

The short allele in a variable repeat sequence of the promoter region of the serotonin transporter gene (5-HTTLPR) has been associated with stronger activation in brain regions critical for processing emotional stimuli. The authors examined whether variants of the 5-HTTLPR promoter polymorphism were also associated with individual differences in attentional biases for emotional stimuli. Words related to anxious and dysphoric emotional states were presented to psychiatric inpatients in a standard dot-probe reaction time task. Compared with participants with two long alleles, carriers of the short 5-HTTLPR allele exhibited a stronger attentional bias for anxious word stimuli. No genetic group difference was observed for dysphoric word stimuli. Findings from this preliminary study highlight the potential for integrating genetic and cognitive models of psychopathology.     

Negative cognitive response to a sad mood induction: Associations with polymorphisms of the serotonin transporter (5-HTTLPR) gene

Increased negative thinking in response to sad mood states has been identified as a marker of depression risk. The present study examined whether polymorphisms of the serotonin transporter (5-HTTLPR) gene were associated with the tendency to endorse negative cognition after sad or neutral mood inductions in a healthy college student sample. Non-depressed participants were genotyped for the 5-HTTLPR and then viewed films designed to elicit a sad mood (n=30) or a neutral mood (n=23). Analyses indicated that individuals homozygous for the short 5-HTTLPR allele endorsed more negative cognition following a sad mood induction than individuals homozygous for the long 5-HTTLPR allele. Negative cognition did not vary as a function of 5-HTTLPR genetic status in the neutral mood condition. These preliminary results suggest that genetic variation of the serotonin transporter may contribute to depression vulnerability via a tendency to think more negatively in response to events that elicit sad mood.     

The DRD4 VNTR polymorphism moderates craving after alcohol consumption.

Recent research has suggested that alterations in mesolimbic dopamine neurotransmission are central to the development and expression of craving for alcohol. Because the D4 dopamine receptor gene, variable numbers of tandem repeats (DRD4 VNTR) polymorphism putatively expresses functional differences in dopamine receptors, the present study tested whether this polymorphism influences the effects of a priming dose of alcohol on craving. Participants consumed 3 alcoholic drinks or 3 control drinks and completed measures of craving after each drink. Participants who were homozygous or heterozygous for the 7 (or longer) repeat allele were classified as DRD4 L, whereas the other participants were classified as DRD4 S. Results suggested that DRD4 L participants demonstrated significantly higher craving after consumption of alcohol as compared with the control beverage.     

Therapygenetics: moving towards personalized psychotherapy treatment

New research suggests that genetic variation predicts response to cognitive behavior therapy (CBT) for the treatment of pediatric anxiety. We discuss this intriguing finding, review its implications for understanding the etiology of psychopathology, and suggest that psychosocial treatment research would strongly benefit from routinely assessing genetic variation in clinical trials.     

Population stratification in the candidate gene study: fatal threat or red herring?

Advances in molecular genetics have provided behavioral scientists with a means of investigating the influence of genetic factors on human behavior. Unfortunately, recent candidate gene studies have produced inconsistent results, and a frequent scapegoat for the lack of replication across studies is the threat of population stratification. This review of the literature on population stratification suggests that the threat may be a red herring. Reliable findings will require improved specification and measurement of the behavioral phenotypes in question, a renewed focus on internal validity, and the specification and testing of genetic factors in the context of longitudinal multivariate models. In this respect, behavioral scientists are well suited to investigating genetic factors that influence psychological mechanisms.     

Conducting a Pragmatic Trial in Integrated Primary Care: Key Decision Points and Considerations

Pragmatic trials testing the effectiveness of interventions under “real world” conditions help bridge the research-to-practice gap. Such trial designs are optimal for studying the impact of implementation efforts, such as the effectiveness of integrated behavioral health clinicians in primary care settings. Formal pragmatic trials conducted in integrated primary care settings are uncommon, making it difficult for researchers to anticipate the potential pitfalls associated with balancing scientific rigor with the demands of routine clinical practice. This paper is based on our experience conducting the first phase of a large, multisite, pragmatic clinical trial evaluating the implementation and effectiveness of behavioral health consultants treating patients with chronic pain using a manualized intervention, brief cognitive behavioral therapy for chronic pain (BCBT-CP). The paper highlights key choice points using the PRagmatic-Explanatory Continuum Indicator Summary (PRECIS-2) tool. We discuss the dilemmas of pragmatic research that we faced and offer recommendations for aspiring integrated primary care pragmatic trialists.

     

Brooding Rumination and Risk for Depressive Disorders in Children of Depressed Mothers

The goal of the current study was to examine the role of brooding rumination in children at risk for depression. We found that children of mothers with a history of major depression exhibited higher levels of brooding rumination than did children of mothers with no depression history. Examining potential mechanisms of this risk, we found no evidence for shared genetic influences (BDNF or 5-HTTLPR) or modeling of mothers’ rumination. However, we did find that children with a history of prior depressive disorders exhibited higher current levels of brooding rumination than children with no depression history. Importantly, children’s brooding predicted prospective onsets of new depressive episodes over a 20-month follow-up even when we statistically controlled for depressive symptom levels at the initial assessment, suggesting that the predictive effect of brooding rumination in children was not due simply to co-occurring depressive symptoms.